Our earlier work on the problem of contrast media reactions had led us to the discovery of a distinct, significant difference in the plasmas of persons who have had severe reactions to contrast media compared to non-reactors. Specifically, under defined conditions in vitro, the rate of activation of the contact (intrinsic) system is substantially greater for reactors. This is manifested by the rate of appearance of kallikrein activity in the presence of the activator dextran sulfate at OC. Our studies to date strongly suggest a significant role for endogenous heparin in this difference. Also, steroid therapy induces changes in levels of contact factors and CI-esterase inhibitor. Our long-term objectives are: the development, based on the above-mentioned findings, of a clinically applicable test for the identification of those in the patient population most at risk of serious contract media reaction; elucidation of the fundamental biochemical causes of the difference in contact system reactivity and the application of that knowledge to prophylaxis and treatment; elucidation of the interrelationships between corticosteroid activity, heparin, and the contact system as they bear on this and other clinical problems. Specific aims include: a prospective study of plasma and serum samples of reactors and non-reactors; refinement of the prekallikrein activation rate test; further study of the role of Cl-esterase inhibitor; exploration of the biochemical basis for the differences found in prekallikrein activation rates; study of the interrelationships of corticosteroid effects, heparin effects, and the contact system. Methodology includes: chromogenic, potentiometric, and other enzyme assays; clotting tests; immunoassays; gel electrophoresis; column chromatography; blood cell counting; platelet aggregation; histological examination by fluorescence microscopy.